Aripiprazole: A Novel Atypical Antipsychotic Drug With a Uniquely Robust Pharmacology

Abstract

Aripiprazole (Abilify ® ) is an atypical antipsychotic drug that has been recently introduced for clinical use in the treatment of schizophrenia. Aripiprazole has a unique pharmacologic profile that includes partial agonism at several G-protein coupled receptors (GPCRs) [especially dopamine (D 2 ) and 5-HT 1A ] and antagonistic action at others (especially 5-HT 2A ). Clinical trials indicate that aripiprazole is effective in treating the positive and negative symptoms of schizophrenia. In short-term studies rapid onset of action (within one week) has been demonstrated. Preliminary data indicate that aripiprazole may also be effective in the treatment of manic symptoms of bipolar disorder. At recommended doses, aripiprazole appears to be safe and well tolerated in most adult patients with schizophrenia and schizoaffective disorder. There is only limited information available on the use of aripiprazole in children and adolescents, and pilot data suggest that a revised dosing strategy, based on weight, is indicated in this population. In the long-term studies, the use of aripiprazole was associated with continued efficacy, good compliance and increased time-to-relapse.Aripiprazole represents the first functionally selective atypical antipsychotic drug.

Pharmacologic analysis of non-synonymous coding h5-HT2A SNPs reveals alterations in atypical antipsychotic and agonist efficacies

“…The clinical relevance for this loss of potency at the 5-HT 2A receptor is currently unclear, although it could be related to side effects (e.g., agitation, insomnia) that are seen early in the course of aripiprazole therapy. 38 Our data would predict that individuals with the T25N polymorphism would be less susceptible to agitation and insomnia -assuming these side effects are related in a causal way to 5-HT 2A agonism.…”

The Evolution of Drug Development in Schizophrenia: Past Issues and Future Opportunities

“…Since chlorpromazine was introduced in 1952, about 50 additional antipsychotic drugs have been developed for the treatment of schizophrenia. Each of these drugs exerts therapeutic action at the dopamine D2 receptor and all but aripiprazole, are antagonists at the D2 receptor (Carlsson and Lindqvist, 1963;Kapur and Mamo, 2003;Davies et al, 2004). Aripiprazole, on the other hand, is a partial agonist at the D2 receptor (for review see Tamminga and Carlsson, 2002).…”

Aripiprazole has Functionally Selective Actions at Dopamine D2 Receptor-Mediated Signaling Pathways

“…Until recently, all of the antipsychotic drugs (APDs), whether 'typical' or 'atypical', or whether of high or low affinity, have been functional D 2 antagonists (Miyamoto et al, 2000;Davies et al, 2004;Maudsley et al, 2005). A clear exception to this, however, is the recently approved compound aripiprazole (Abilify).…”